ADAR - Wikipedia

ADAR, ADAR1, ADAR2, ADAR3, ADARB1, ADARB2, ADAR1p150, ADAR1p110, IFI-4, DSH, P136, adenosine deaminase RNA specific, DRADA, IFI4, AGS6, G1P1, K88DSRBP, DSRAD. ADAR FromWikipedia,thefreeencyclopedia Jumptonavigation Jumptosearch MammalianproteinfoundinHomosapiens Forotheruses,seeAdar(disambiguation). ADARAvailablestructuresPDBOrthologsearch:PDBeRCSBListofPDBidcodes1QBJ,1QGP,1XMK,2ACJ,2GXB,2L54,2MDR,3F21,3F22,3F23,3IRQ,3IRRIdentifiersAliasesADAR,ADAR1,ADAR2,ADAR3,ADARB1,ADARB2,ADAR1p150,ADAR1p110,IFI-4,DSH,P136,adenosinedeaminaseRNAspecific,DRADA,IFI4,AGS6,G1P1,K88DSRBP,DSRADExternalIDsOMIM:146920MGI:1889575HomoloGene:9281GeneCards:ADARGenelocation(Human)Chr.Chromosome1(human)[1]Band1q21.3Start154,581,695bp[1]End154,628,013bp[1]Genelocation(Mouse)Chr.Chromosome3(mouse)[2]Band3|3F1Start89,622,329bp[2]End89,660,753bp[2]RNAexpressionpatternBgeeTopexpressedin endothelialcell middletemporalgyrus middlefrontalgyrus visceralpleura parietalpleura palpebralconjunctiva thymus internalglobuspallidus Brodmannarea23 parotidglandMorereferenceexpressiondataBioGPSMorereferenceexpressiondataGeneontologyMolecularfunction DNAbinding metalionbinding double-strandedRNAadenosinedeaminaseactivity adenosinedeaminaseactivity GO:0001948proteinbinding hydrolaseactivity RNAbinding double-strandedRNAbinding tRNA-specificadenosinedeaminaseactivity Cellularcomponent cytoplasm membrane supraspliceosomalcomplex nucleoplasm nucleolus nucleus Biologicalprocess hematopoieticstemcellhomeostasis cellularresponsetovirus miRNAloadingontoRISCinvolvedingenesilencingbymiRNA RNAprocessing proteinimportintonucleus immunesystemprocess negativeregulationoftypeIinterferon-mediatedsignalingpathway mRNAprocessing responsetovirus baseconversionorsubstitutionediting negativeregulationofapoptoticprocess inuteroembryonicdevelopment pre-miRNAprocessing negativeregulationofviralgenomereplication defenseresponsetovirus typeIinterferonsignalingpathway osteoblastdifferentiation hematopoieticprogenitorcelldifferentiation proteinexportfromnucleus responsetointerferon-alpha negativeregulationofproteinkinaseactivitybyregulationofproteinphosphorylation erythrocytedifferentiation somaticdiversificationofimmunereceptorsviasomaticmutation definitivehemopoiesis positiveregulationofviralgenomereplication negativeregulationofRNAinterference genesilencing innateimmuneresponse adenosinetoinosineediting productionofmiRNAsinvolvedingenesilencingbymiRNA Sources:Amigo/QuickGOOrthologsSpeciesHumanMouseEntrez10356417EnsemblENSG00000160710ENSMUSG00000027951UniProtP55265Q99MU3RefSeq(mRNA)NM_001025107NM_001111NM_001193495NM_015840NM_015841NM_001365045NM_001365046NM_001365047NM_001365048NM_001365049NM_001038587NM_001146296NM_019655NM_001357958RefSeq(protein)NP_001020278NP_001102NP_001180424NP_056655NP_056656NP_001033676NP_001139768NP_062629NP_001344887Location(UCSC)Chr1:154.58–154.63MbChr3:89.62–89.66MbPubMedsearch[3][4]WikidataView/EditHumanView/EditMouse Thedouble-strandedRNA-specificadenosinedeaminaseenzymefamilyareencodedbytheADARfamilygenes.[5]ADARstandsforadenosinedeaminaseactingonRNA.[6][7]ThisarticlefocusesontheADARproteins;Thisarticledetailstheevolutionaryhistory,structure,function,mechanismsandimportanceofallproteinswithinthisfamily.[5] ADARenzymesbindtodouble-strandedRNA(dsRNA)andconvertadenosinetoinosine(hypoxyanthine)bydeamination.[8]ADARproteinsactpost-transcriptionally,changingthenucleotidecontentofRNA.[9]Theconversionfromadenosinetoinosine(AtoI)intheRNAdisruptsthenormalA:Upairing,destabilizingtheRNA.Inosineisstructurallysimilartoguanine(G)whichleadstoinosinetocytosine(I:C)binding.[10]Inosinetypicallymimicsguanosineduringtranslationbutcanalsobindtouracil,cytosine,andadenosine,thoughitisnotfavored. CodonchangesmayarisefromRNAeditingleadingtochangesinthecodingsequencesforproteinsandtheirfunctions.[11]MosteditingsitesarefoundinnoncodingregionsofRNAsuchasuntranslatedregions(UTRs),Aluelements,andlonginterspersednuclearelements(LINEs).[12]Codonchangescangiverisetoalternatetranscriptionalsplicevariants.ADARimpactsthetranscriptomeinediting-independentways,likelybyinterferingwithotherRNA-bindingproteins.[9] MutationsinthisgeneareassociatedwithseveraldiseasesincludingHIV,measles,andmelanoma.RecentresearchsupportsalinkagebetweenRNA-editingandnervoussystemdisorderssuchasamyotrophiclateralsclerosis(ALS).AtypicalRNAeditinglinkedtoADARmayalsocorrelatetomentaldisorderssuchasschizophrenia,epilepsy,andsuicidaldepression.[13] Contents 1Discovery 2Evolutionandfunction 3Enzymeclassification 4Catalyticactivity 4.1Biochemicalreaction 4.2Activesite 4.3Dimerization 5Modelorganisms 6Roleindisease 6.1Aicardi–GoutièresSyndromeandbilateralstriatalnecrosis/dystonia 6.2AmyotrophicLateralSclerosis(ALS) 6.3Cancer 6.3.1Hepatocellularcarcinoma 6.3.2Melanoma 6.4Dyschromatosissymmetricahereditaria(DSH1) 6.5HIV 7Viralactivity 7.1Antiviral 7.2Proviral 8Seealso 9References 10Furtherreading 11Externallinks Discovery[edit] TheADARenzymeanditsassociatedgenewerediscoveredaccidentallyin1987asaresultofresearchbyBrendaBassandHaroldWeintraub.[14]TheseresearcherswereusingantisenseRNAinhibitiontodeterminewhichgenesplayakeyroleinthedevelopmentofXenopuslaevisembryos.PreviousresearchonXenopusoocyteswassuccessful.However,whenBassandWeintraubappliedidenticalprotocolstoXenopusembryos,theywereunabletodeterminetheembryo’sdevelopmentalgenes.Tounderstandwhythemethodwasunsuccessful,theybegancomparingduplexRNAinbothoocytesandembryos.ThisledthemtodiscoveradevelopmentallyregulatedactivitythatdenaturesRNA:RNAhybridsinembryos. In1988,RichardWagneretal.furtherstudiedtheactivityoccurringonXenopusembryos.[15]TheydeterminedaproteinwasresponsibleforunwindingofRNAduetotheabsenceofactivityafterproteinasetreatment.ThisproteinisspecificfordsRNAanddoesnotrequireATP.Itbecameevidentthisprotein’sactivityondsRNAmodifiesitbeyondapointofrehybridizationbutdoesnotfullydenatureit.Finally,theresearchersdeterminedthisunwindingisduetothedeaminationofadenosineresiduestoinosine.Thismodificationresultsinmismatchedbase-pairingbetweeninosineanduridine,leadingtothedestabilizationandunwindingofdsRNA. Evolutionandfunction[edit] ADARsareoneofthemostcommonformsofRNAediting,andhavebothselectiveandnon-selectiveactivity.[16]ADARisabletomodifyandregulatetheoutputofgeneproduct,asinosineisinterpretedbythecelltobeguanosine.ADARcanchangethefunctionalityofsmallRNAmolecules.Recently,ADARshavealsobeendiscoveredasaregulatoronsplicingandcircRNAbiogenesiswiththeireditingcapabilityorRNAbindingfunction.[17][18][19]ItisbelievedthatADARevolvedfromADAT(AdenosineDeaminaseActingontRNA),acriticalproteinpresentinalleukaryotes,earlyinthemetazoanperiodthroughtheadditionofadsRNAbindingdomain.ThislikelyoccurredinthelineagewhichleadstothecrownMetazoa.WhenaduplicateADATgenewascoupledtoanothergenewhichencodedatleastonedoublestrandedRNAbinding.TheADARfamilyofgeneshasbeenlargelyconservedoverthehistoryofitsexistence.This,alongwithitspresenceinthemajorityofmodernphyla,indicatesthatRNAeditingisessentialinregulatinggenesformetazoanorganisms.ADARhasnotbeendiscoveredinavarietyofnon-metazoaneukaryotes,suchasplants,fungiandchoanoflagellates. ADARsaresuggestedtohavetwofunctions:toincreasediversityoftheproteomebyinducingcreationofharmlessnon-genomicallyencodedproteins,andprotectingcrucialtranslationalsites.Theconventionalbeliefistheirprimaryroleistoincreasethediversityoftranscriptsandexpandtheproteinvariation,promotingevolutionofproteins.[5] Enzymeclassification[edit] Inmammals,therearethreetypesofADARenzymes,ADAR(ADAR1),ADARB1(ADAR2)andADARB2(ADAR3).[20]ADARandADARB1arefoundinmanytissuesinthebodywhileADARB2isonlyfoundinthebrain.[11]ADARandADARB1areknowntobecatalyticallyactivewhileevidencesuggestsADARB2isinactive.[11]ADARhastwoknownisoforms,ADAR1p150andADAR1p110.ADAR1p110istypicallyfoundinthenucleuswhileADAR1p150shufflesbetweenthenucleusandthecytoplasm,mostlypresentinthecytoplasm.[20]ADARandADARB1sharefunctionaldomainsandhavesimilarexpressionpatterns,structureofproteins,andrequiresubstratedoublestrandedRNAstructures.However,theydifferintheireditingactivity.[21] Catalyticactivity[edit] Biochemicalreaction[edit] ADARscatalyzethehydrolyticdeaminationreactionfromadenosinetoinosine.[8]Anactivatedwatermoleculewillreactwithadenosineinanucleophilicsubstitutionreactionwiththecarbon-6aminegroup.Ahydratedintermediatewillexistforashortperiodoftime,thentheaminegroupwillleaveasanammoniaion. AdenosineconversiontoInosineviaADAR Activesite[edit] Inhumans,ADARenzymeshavetwotothreeamino-terminaldsRNAbindingdomains(dsRBDs),andonecarboxyterminalcatalyticdeaminasedomain.[20]InthedsRBDthereisaconservedα-β-β-β-αconfiguration.[11]ADAR1containstwoareasforbindingZ-DNAknownasZαandZβ.ADAR2andADAR3haveanargininerichsinglestrandedRNA(ssRNA)bindingdomain.AcrystalstructureofADAR2hasbeensolved.[20]Intheenzymeactivesite,thereisaglutamicacidresidue(E396)thathydrogenbondstoawater.Ahistidine(H394)andtwocysteineresidues(C451andC516)coordinatewithazincion.Thezincactivatesthewatermoleculeforthenucleophilichydrolyticdeamination.Withinthecatalyticcorethereisaninositolhexakisphosphate(IP6),whichstabilizesarginineandlysineresidues. Dimerization[edit] InmammalstheconversionfromAtoIrequireshomodimerizationofADAR1andADAR2,butnotADAR3.[11]InvivostudieshavearenotconclusiveifRNAbindingisrequiredfordimerization.AstudywithADARfamilymutantsshowedthemutantswerenotabletobindtodsRNAbutwerestillabletodimerize,suggestingtheymaybindbasedonprotein-proteininteractions.[11][22] Modelorganisms[edit] ModelorganismshavebeenusedinthestudyofADARfunction.Aconditionalknockoutmouseline,calledAdartm1a(EUCOMM)Wtsi[23][24]wasgeneratedaspartoftheInternationalKnockoutMouseConsortiumprogram—ahigh-throughputmutagenesisprojecttogenerateanddistributeanimalmodelsofdiseasetointerestedscientists.[25][26][27]Maleandfemalemiceunderwentastandardizedphenotypicscreentodeterminetheeffectsofdeletion.[28][29]Twentyfivetestswerecarriedoutonthemutantsandtwosignificantabnormalitieswereobserved.[6]Fewhomozygousmutantembryoswereidentifiedduringgestation,andnonesurviveduntilweaning.Theremainingtestswerecarriedoutonheterozygousmutantadultmiceandnoabnormalitieswereobservedintheseanimals.[28] Roleindisease[edit] Aicardi–GoutièresSyndromeandbilateralstriatalnecrosis/dystonia[edit] ADAR1isoneofmultiplegeneswhichoftencontributetoAicardi–Goutièressyndromewhenmutated.[30]Aicardi–GoutièressyndromeisageneticinflammatorydiseaseprimarilyaffectingtheskinandthebrainanditischaracterizedbyhighlevelsofIFN-αincerebralspinalfluid.[31]Theinflammationiscausedbyincorrectactivationofinterferoninduciblegenessuchasthoseactivatedtofightoffviralinfections.MutationandlossoffunctionofADAR1preventsdestabilizationofdoublestrandedRNA(dsRNA).[32]ThisbuildupofdsRNAstimulatesIFNproductionwithoutaviralinfection,causinganinflammatoryreactionandautoimmuneresponse.[33]Thephenotypeintheknock-outmiceisrescuedbythep150formofADAR1containingtheZαdomainthatbindsspecificallytotheleft-handeddouble-strandedconformationfoundinZ-DNAandZ-RNA,butnotbythep110isoformlackingthisdomain.[34]Inhumans,theP193AmutationintheZαdomainiscausalforAicardi–Goutièressyndrome[30]andforthemoreseverephenotypefoundinBilateralStriatalNecrosis/Dystonia.[35]Thefindingsestablishabiologicalrolefortheleft-handedZ-DNAconformation.[36] AmyotrophicLateralSclerosis(ALS)[edit] Inmotorneurons,themostwell-groundedmarkerofamyotrophiclateralsclerosis(ALS)istheTARDNA-bindingprotein(TDP-43).WhenthereisfailureofRNA-editingduetodownregulationofTDP-43,motorneuronsdevoidofADAR2enzymesexpressunregulated,leadingtoabnormallypermeableCa2+channels.ADAR2knockoutmiceshowsignsofALSphenotypesimilarity.CurrentresearchersaredevelopingamoleculartargetingtherapybynormalizingexpressionofADAR2.[37] Cancer[edit] (ADAR)-inducedA-to-IRNAeditingmayelicitdangerousaminoacidmutations.EditingmRNAtypicallyimpartsmissensemutationsleadingtoalterationsinthebeginningandterminatingregionsoftranslation.However,crucialaminoacidchangescanoccur,resultinginchangeoffunctionofseveralcellularprocesses.Aminoacidchangescanresultinproteinstructuralchangesatsecondary,tertiary,andquaternarystructures.ResearchersobservedhighlevelsofoncogeneticA-to-IeditingincircularRNAprecursors,directlyconfirmingADAR'srelationshiptocancer.AlistoftumorrelatedRNAeditingsitescanbefoundhere.[38] Hepatocellularcarcinoma[edit] Studiesofpatientswithhepatocellularcarcinoma(HCC)haveshowntrendsofupregulatedADAR1anddownregulatedADAR2.ResultssuggesttheirregularregulationisresponsibleforthedisruptedAtoIeditingpatternseeninHCCandthatADAR1actsasanoncogeneinthiscontextwhilstADAR2hastumorsuppressoractivities.[39]TheimbalanceinADARexpressioncouldchangethefrequencyofAtoItransitionsintheproteincodingregionofgenes,resultinginmutatedproteinswhichdrivethedisease.ThedysregulationofADAR1andADAR2couldbeusedasapossibleprognosticmarker. Melanoma[edit] StudieshaveindicatedthatlossofADAR1contributestomelanomagrowthandmetastasis.ADARenzymescanactonmicroRNAandaffectitsbiogenesis,stabilityand/oritsbindingtarget.[40]ADAR1maybedownregulatedbycAMP-responseelementbindingprotein(CREB),limitingitsabilitytoactonmiRNA.[41]OnesuchexampleismiR-455-5pwhichiseditedbyADAR1.WhenADARisdownregulatedbyCREBtheuneditedmiR-455-5pdownregulatesatumorsuppressorproteincalledCPEB1,contributingtomelanomaprogressioninaninvivomodel. Dyschromatosissymmetricahereditaria(DSH1)[edit] AGly1007ArgmutationinADAR1,aswellasothertruncatedversions,havebeenimplicatedasacauseinsomecasesofDSH1.[42]ThisisadiseasecharacterizedbyhyperpigmentationinthehandsandfeetandcanoccurinJapaneseandChinesefamilies. HIV[edit] ExpressionlevelsoftheADAR1proteinhaveshowntobeelevatedduringHIVinfectionandithasbeensuggestedthatitisresponsibleforAtoGmutationsintheHIVgenome,inhibitingreplication.[43]ThemutationintheHIVgenomebyADAR1mightinsomecasesleadtobeneficialviralmutationswhichcouldcontributetodrugresistance. [41] Viralactivity[edit] Antiviral[edit] ADAR1isaninterferon(IFN)-inducibleprotein(onereleasedbyacellinresponsetoapathogenorvirus),abletoassistinacell’simmunepathway.EvidenceshowseliminationofHCVreplicon,LymphocyticchoriomeningitisLCMV,andpolyomavirus.[44][45] Proviral[edit] ADAR1isproviralinothercircumstances.ADAR1’sAtoIeditinghasbeenfoundinmanyvirusesincludingmeaslesvirus,[46][45][47]influenzavirus,[48]lymphocyticchoriomeningitisvirus,[49]polyomavirus,[50]hepatitisdeltavirus,[51]andhepatitisCvirus.[52]AlthoughADAR1hasbeenseeninotherviruses,ithasonlybeenstudiedextensivelyinafew.ResearchonmeaslesvirusshowsADAR1enhancingviralreplicationthroughtwodifferentmechanisms:RNAeditingandinhibitionofdsRNA-activatedproteinkinase(PKR).[44][45]Specifically,virusesarethoughttouseADAR1asapositivereplicationfactorbyselectivelysuppressingdsRNA-dependentandantiviralpathways.[53] Seealso[edit] RNAediting PotassiumchannelRNAeditingsignal ADARB1 Z-DNA References[edit] 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Furtherreading[edit] ValenzuelaA,BlancoJ,CallebautC,JacototE,LluisC,HovanessianAG,FrancoR(1997)."HIV-1envelopegp120andviralparticlesblockadenosinedeaminasebindingtohumanCD26".CellularPeptidasesinImmuneFunctionsandDiseases.AdvancesinExperimentalMedicineandBiology.Vol. 421.pp. 185–92.doi:10.1007/978-1-4757-9613-1_24.ISBN 978-1-4757-9615-5.PMID 9330696. WatheletMG,SzpirerJ,NolsCB,ClaussIM,DeWitL,IslamMQ,et al.(September1988)."CloningandchromosomallocationofhumangenesinduciblebytypeIinterferon".SomaticCellandMolecularGenetics.14(5):415–426.doi:10.1007/BF01534709.PMID 3175763.S2CID 42406993. WangY,ZengY,MurrayJM,NishikuraK(November1995)."GenomicorganizationandchromosomallocationofthehumandsRNAadenosinedeaminasegene:theenzymeforglutamate-activatedionchannelRNAediting".JournalofMolecularBiology.254(2):184–195.doi:10.1006/jmbi.1995.0610.PMID 7490742. PattersonJB,SamuelCE(October1995)."Expressionandregulationbyinterferonofadouble-stranded-RNA-specificadenosinedeaminasefromhumancells:evidencefortwoformsofthedeaminase".MolecularandCellularBiology.15(10):5376–5388.doi:10.1128/mcb.15.10.5376.PMC 230787.PMID 7565688. PattersonJB,ThomisDC,HansSL,SamuelCE(July1995)."Mechanismofinterferonaction:double-strandedRNA-specificadenosinedeaminasefromhumancellsisinduciblebyalphaandgammainterferons".Virology.210(2):508–511.doi:10.1006/viro.1995.1370.PMID 7618288. O'ConnellMA,KrauseS,HiguchiM,HsuanJJ,TottyNF,JennyA,KellerW(March1995)."CloningofcDNAsencodingmammaliandouble-strandedRNA-specificadenosinedeaminase".MolecularandCellularBiology.15(3):1389–1397.doi:10.1128/mcb.15.3.1389.PMC 230363.PMID 7862132. WeierHU,GeorgeCX,GreulichKM,SamuelCE(November1995)."Theinterferon-inducible,double-strandedRNA-specificadenosinedeaminasegene(DSRAD)mapstohumanchromosome1q21.1-21.2".Genomics.30(2):372–375.doi:10.1006/geno.1995.0034.PMID 8586444. LiuY,GeorgeCX,PattersonJB,SamuelCE(February1997)."Functionallydistinctdouble-strandedRNA-bindingdomainsassociatedwithalternativesplicesitevariantsoftheinterferon-inducibledouble-strandedRNA-specificadenosinedeaminase".TheJournalofBiologicalChemistry.272(7):4419–4428.doi:10.1074/jbc.272.7.4419.PMID 9020165. ValenzuelaA,BlancoJ,CallebautC,JacototE,LluisC,HovanessianAG,FrancoR(April1997)."AdenosinedeaminasebindingtohumanCD26isinhibitedbyHIV-1envelopeglycoproteingp120andviralparticles".JournalofImmunology.158(8):3721–3729.PMID 9103436. HerbertA,AlfkenJ,KimYG,MianIS,NishikuraK,RichA(August1997)."AZ-DNAbindingdomainpresentinthehumaneditingenzyme,double-strandedRNAadenosinedeaminase".ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.94(16):8421–8426.Bibcode:1997PNAS...94.8421H.doi:10.1073/pnas.94.16.8421.PMC 22942.PMID 9237992. LiuY,HerbertA,RichA,SamuelCE(July1998)."Double-strandedRNA-specificadenosinedeaminase:nucleicacidbindingproperties".Methods.15(3):199–205.doi:10.1006/meth.1998.0624.PMID 9735305. GeorgeCX,SamuelCE(April1999)."HumanRNA-specificadenosinedeaminaseADAR1transcriptspossessalternativeexon1structuresthatinitiatefromdifferentpromoters,oneconstitutivelyactiveandtheotherinterferoninducible".ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.96(8):4621–4626.Bibcode:1999PNAS...96.4621G.doi:10.1073/pnas.96.8.4621.PMC 16382.PMID 10200312. SchwartzT,RouldMA,LowenhauptK,HerbertA,RichA(June1999)."CrystalstructureoftheZalphadomainofthehumaneditingenzymeADAR1boundtoleft-handedZ-DNA".Science.284(5421):1841–1845.doi:10.1126/science.284.5421.1841.PMID 10364558. SchadeM,TurnerCJ,KühneR,SchmiederP,LowenhauptK,HerbertA,et al.(October1999)."ThesolutionstructureoftheZalphadomainofthehumanRNAeditingenzymeADAR1revealsaprepositionedbindingsurfaceforZ-DNA".ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesofAmerica.96(22):12465–12470.Bibcode:1999PNAS...9612465S.doi:10.1073/pnas.96.22.12465.PMC 22950.PMID 10535945. BlancoJ,ValenzuelaA,HerreraC,LluísC,HovanessianAG,FrancoR(July2000)."TheHIV-1gp120inhibitsthebindingofadenosinedeaminasetoCD26byamechanismmodulatedbyCD4andCXCR4expression".FEBSLetters.477(1–2):123–128.doi:10.1016/S0014-5793(00)01751-8.PMID 10899322. HerreraC,MorimotoC,BlancoJ,MallolJ,ArenzanaF,LluisC,FrancoR(June2001)."ComodulationofCXCR4andCD26inhumanlymphocytes".TheJournalofBiologicalChemistry.276(22):19532–19539.doi:10.1074/jbc.M004586200.PMID 11278278. WongSK,SatoS,LazinskiDW(June2001)."SubstraterecognitionbyADAR1andADAR2".RNA.7(6):846–858.doi:10.1017/S135583820101007X.PMC 1370134.PMID 11421361. EckmannCR,NeunteuflA,PfaffstetterL,JantschMF(July2001)."ThehumanbutnottheXenopusRNA-editingenzymeADAR1hasanatypicalnuclearlocalizationsignalanddisplaysthecharacteristicsofashuttlingprotein".MolecularBiologyoftheCell.12(7):1911–1924.doi:10.1091/mbc.12.7.1911.PMC 55639.PMID 11451992. YangS,DengP,ZhuZ,ZhuJ,WangG,ZhangL,et al.(October2014)."AdenosinedeaminaseactingonRNA1limitsRIG-IRNAdetectionandsuppressesIFNproductionrespondingtoviralandendogenousRNAs".JournalofImmunology.193(7):3436–3445.doi:10.4049/jimmunol.1401136.PMC 4169998.PMID 25172485. Externallinks[edit] OMIMentriesonDyschromatosisSymmetricaHereditaria1 ADARhumangenelocationintheUCSCGenomeBrowser. ADARhumangenedetailsintheUCSCGenomeBrowser. vtePDBgallery 1qbj:CRYSTALSTRUCTUREOFTHEZALPHAZ-DNACOMPLEX 1qgp:NMRSTRUCTUREOFTHEZ-ALPHADOMAINOFADAR1,15STRUCTURES 1xmk:TheCrystalstructureoftheZbdomainfromtheRNAeditingenzymeADAR1 2acj:CrystalstructureoftheB/ZjunctioncontainingDNAboundtoZ-DNAbindingproteins 2gxb:CrystalStructureofTheZaDomainboundtoZ-RNA vteHydrolases:carbon-nitrogennon-peptide(EC3.5)3.5.1:Linearamides/Amidohydrolases Asparaginase Glutaminase Urease Biotinidase Aminoacylase ACY1 Aspartoacylase(ACY2) ACY3 Ceramidase Aspartylglucosaminidase Fattyacidamidehydrolase Histonedeacetylase Sirtuin 3.5.2:Cyclicamides/Amidohydrolases Barbiturase Beta-lactamase Dihydroorotase 3.5.3:Linearamidines/Ureohydrolases Arginase Agmatinase Protein-argininedeiminase 3.5.4:Cyclicamidines/Aminohydrolases Guaninedeaminase Adenosinedeaminase AMPdeaminase Inosinemonophosphatesynthase DCMPdeaminase GTPcyclohydrolaseI Cytidinedeaminase AICDA Activation-inducedcytidinedeaminase 3.5.5:Nitriles/Aminohydrolases Nitrilase 3.5.99:Other Riboflavinase ThiaminaseII vteEnzymesActivity Activesite Bindingsite Catalytictriad Oxyanionhole Enzymepromiscuity Diffusion-limitedenzyme Coenzyme Cofactor Enzymecatalysis Regulation Allostericregulation Cooperativity Enzymeinhibitor Enzymeactivator Classification ECnumber Enzymesuperfamily Enzymefamily Listofenzymes Kinetics Enzymekinetics Eadie–Hofsteediagram Hanes–Woolfplot Lineweaver–Burkplot Michaelis–Mentenkinetics Types EC1Oxidoreductases(list) EC2Transferases(list) EC3Hydrolases(list) EC4Lyases(list) EC5Isomerases(list) EC6Ligases(list) EC7Translocases(list) Portal: Biology Retrievedfrom"https://en.wikipedia.org/w/index.php?title=ADAR&oldid=1089594423" Categories:Genesonhumanchromosome1EC3.5.4GenesmutatedinmiceHiddencategories:ArticleswithshortdescriptionShortdescriptionmatchesWikidata Navigationmenu Personaltools NotloggedinTalkContributionsCreateaccountLogin Namespaces ArticleTalk English Views ReadEditViewhistory More Search Navigation MainpageContentsCurrenteventsRandomarticleAboutWikipediaContactusDonate Contribute HelpLearntoeditCommunityportalRecentchangesUploadfile Tools WhatlinkshereRelatedchangesUploadfileSpecialpagesPermanentlinkPageinformationCitethispageWikidataitem Print/export DownloadasPDFPrintableversion Languages CymraegDeutsch日本語TürkçeУкраїнська Editlinks